Abstract

Due to the inherent disadvantage of biomarker dilution in complex biological fluids such as serum/plasma, urine, and saliva, investigative studies directed at tissues obtained from the primary site of pathology probably afford the best opportunity for the discovery of disease biomarkers. Still, the large variation of protein relative abundances with clinical specimens often exceeds the dynamic range of currently available proteomic techniques. Furthermore, since the sizes of human tissue biopsies are becoming significantly smaller due to the advent of minimally invasive methods and early detection and treatment of lesions, a more effective discovery-based proteomic technology is critically needed to enable comprehensive and comparative studies of protein profiles that will have diagnostic and therapeutic relevance.

This review therefore focuses on the most recent advances in capillary electrophoresis-based single and multidimensional separations coupled with mass spectrometry for performing comprehensive proteomic analysis of clinical specimens. In addition to protein identification, monitoring quantitative changes in protein expression is essential for the discovery of disease-associated biomarkers. Comparative proteomics involving measurements in changes of biological pathways or functional processes are further expected to provide relevant markers and networks, molecular relationships among different stages of disease, and molecular mechanisms that drive the progression of disease.

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Notes

Acknowledgment

We thank the National Cancer Institute (CA143177), the National Center for Research Resources (RR032333), and the National Institute of General Medical Sciences (GM103536) for supporting portions of our research activities reviewed in this chapter.